Tacrolimus (also known as FK506) is a neutral macrolide isolated from the fungus Streptomyces tsukubaenis. Tacrolimus has been used clinically as an immunosuppressant in organ transplantation and for treating autoimmune diseases. See Wallemacq et al., “FK 506 (Tacrolimus), a Novel Immunosuppressant in Organ Transplantation: Clinical, Biomedical, and Analytical Aspects,” Clinical Chemistry, 39/11, 2219-2228 (1993). As with many therapeutic drugs, it is desirable to be able to monitor the blood concentrations of tacrolimus quantitatively to ensure proper efficacy of the drug and to protect against possible toxicity during treatment.
A variety of measuring methods have been developed to monitor the blood concentrations of tacrolimus. Many of these methods require the use of a calibration curve for a chemical analyzer by using multiple calibration solutions or calibrators which have been carefully prepared with known, predetermined concentrations of tacrolimus. These calibration or standard solutions may be assayed one or more times and the mean resulting reaction signals are plotted versus their respective known tacrolimus concentrations. A continuous calibration curve may be produced using any of several mathematical techniques chosen to produce an accurate replication of the relationship between a reaction signal and the tacrolimus concentration. For greatest accuracy, calibration curves are established at regular intervals, to compensate for reagent particulars, and on individual analyzers, to compensate for equipment performance.
Several challenges have arisen in the preparation of tacrolimus calibrating and standard compositions. For example, some standard solutions for tacrolimus have are unstable and subject to rapid degradation, leading to inaccurate test results. Furthermore, tacrolimus is insoluble in water, and some standard solutions have included organic solvents that may leave residues or otherwise interfere with the operation or precision of test equipment such as automated analyzers.
Accordingly, there continues to be a need for improved tacrolimus standard compositions.